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dc.creatorLeposavić, Gordana
dc.creatorPešić, Vesna
dc.creatorStojić-Vukanić, Zorica
dc.creatorRadojević, Katarina
dc.creatorArsenović-Ranin, Nevena
dc.creatorKosec, Duško
dc.creatorPerišić, Milica
dc.creatorPilipović, Ivan
dc.date.accessioned2021-02-18T10:35:09Z
dc.date.available2021-02-18T10:35:09Z
dc.date.issued2010
dc.identifier.issn0531-5565
dc.identifier.urihttp://intor.torlakinstitut.com/handle/123456789/296
dc.description.abstractAlpha(1)-adrenoceptors (alpha(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via alpha(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as alpha(1)-AR expression, and 2) then the effects of 14-day-long treatment with the alpha(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via alpha(1)-ARs due to increased NA availability and alpha(1)-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCR alpha beta(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCR alpha beta + cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161 +TCR alpha beta + cells. Thus, the study indirectly suggests an age-associated increase in the basal alpha(1)-AR-mediated inhibitory influence of NA on thymopoiesis. (C) 2010 Elsevier Inc. All rights reserved.en
dc.publisherPergamon-Elsevier Science Ltd, Oxford
dc.relationinfo:eu-repo/grantAgreement/MESTD/MPN2006-2010/145049/RS//
dc.rightsrestrictedAccess
dc.sourceExperimental Gerontology
dc.subjectAgeingen
dc.subjectNoradrenalineen
dc.subjectalpha -adrenoceptorsen
dc.subjectRat thymusen
dc.subjectT-cell developmenten
dc.titleAge-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell developmenten
dc.typearticle
dc.rights.licenseARR
dc.citation.epage935
dc.citation.issue12
dc.citation.other45(12): 918-935
dc.citation.rankM21
dc.citation.spage918
dc.citation.volume45
dc.identifier.doi10.1016/j.exger.2010.08.011
dc.identifier.pmid20800673
dc.identifier.rcubconv_260
dc.identifier.scopus2-s2.0-78449280616
dc.identifier.wos000285368200002
dc.type.versionpublishedVersion


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